The research of anti-bacterial adhesion and its significance is a large field covering different aspects of nature and human life, such as marine science, soil and plant ecology, food industry and most importantly, the biomedical field. Implanted medical devices are of increasing importance in the practice of medicine and currently there are more than 100,000 products in over 1700 categories. It is estimated that more than 3-million people in the United States have long-term implants. However, bacterial adhesion and biofilm formation on medical devices are universal and challenging problems that can lead to complete failure of the implanted devices (Vinh et.al., 2005, J Long Term Eff Med Implants 15: 467-88). Adherence of bacteria to the surfaces of the polymer and subsequent biofilm formation play an important role in pathogenesis of device-related infection (Dibdin et.al., 1999, J. Methods Enzymol, 310: 296-322). Biofilm bacteria can usually survive the use of antiseptics and/or antibiotics at concentration 1000 to 1500 times higher than the concentrations needed to kill planktonic cells of the same species (Costerton, 1999, Int. J. Antimicrob. Agents, 11: 2217-2221). Current strategies for fighting biofilm formation focus on the coating biomaterial surfaces (Poncin-Epaillard, et.al., 2003, J. Biomater. Sci. Polym. Ed. 1005-28); and the incorporation of antimicrobial or antiseptic agents into current polymer biomaterials (Schierholz et, al., 2001, J. Chemother. 13: 239-50) with limited efficacy. So far, there appears to be a limited number of simple and reliable methods to detect anti-adherent efficacy and ‘zero adhesion’ has never been achieved.
An alternative approach for controlling bacterial adhesion is to select active molecules that can block bacterial adhesion, because the adhesion of microorganisms to the inert surfaces is the first step in the development of a wide variety of infections. Since anti-adherent agents are not bactericidal, the propagation and spread of resistant strains is much less likely to occur than as a result of exposure to bactericidal agents. The major drawback of anti-adhesion strategies is that most bacteria possess more than one type of adhesin. Adhesion may also involve factors other than just adhesion-receptor interactions such as hydrophobic and other non-specific interactions that occur under different shear-forces. For anti-adhesion therapy to be effective, either a single agent possessing a broad spectrum of anti-adherent activity, or multiple agents specifically inhibiting each type of adhesin should be applied to the infecting pathogens (Ofek et al. 2003, FEMS Immuno. Med. Microbiol. 15: 181-191).
“One-bead one-compound” (OBOC) combinatorial library concept (Lam, et al. 1991, Nature 354: 82-84) makes it convenient to identify a single agent against multiple adhesins and adherent factors by screening hundred to thousands of compounds with many bacterial strains in parallel. In this method, the library is prepared by a “split-mix synthesis” approach using polystyrene beads as a solid support. As a result, each bead displays only one chemical entity but there are approximately 1013 copies of the same chemical compound on and within one single bead. The exact chemical nature of the compound on selected bead can be determined through the usage of an automatic micro-sequencer. This technology has not only made an impact on the discovery of ligands for both known and unknown receptors on cancer cell lines, but also helped to accelerate the development of anti-cancer therapy (Lam et. al., 1997, Anti-Cancer Drug Design, 12:145-167).